ROLE FOR TOLL-LIKE RECEPTOR 3 IN MUSCLE REGENERATION AFTER CARDIOTOXIN INJURY

Introduction: Sterile tissue injury induces an inflammatory response involving cytokines that have crucial roles in the tissue repair that follows. Methods: MyH3 and type 1 interferon (IFN) were assessed by qPCR after cardiotoxin (CTX)induced muscle injury. Results: CTX-induced injury increased expression of IFN-regulated genes, IFIT1 and MX-2, which was blocked in type 1 IFN receptor (IFNR)-deficient mice. However, IFNR-deficient mice showed no significant differences in muscle regeneration as assessed by MyH3 expression. MyH3 was significantly reduced in TLR3-deficient but not MyD88-deficient mice. TLR3-deficient mice also showed altered expression of proinflammatory cytokines, IL-6, IL-1b, and TNF-alpha. Conclusions: CTX-induced muscle injury increased markers of innate immune activation, but blocking type 1 IFN signaling had no effect on muscle regeneration. Taken together, these results suggest a role for TLR3, and perhaps other innate immune signals, in the inflammatory response to CTX-induced muscle injury and consequent muscle regeneration. Muscle Nerve 43: 733-740, 2011